Abstract

Abstract 2425

Poster Board II-402

Introduction:

Unrelated cord blood transplantation (CBT) is associated with a risk of graft rejection due in part to a limiting cellular content of the CB unit. Increasing the cellular content of the CB unit mitigates the graft rejection risk, but methods to use adjuvant immuno-modulatory cell co-infusions have also been tested with some success. We have investigated the co-infusion of photochemically (psoralen S59) treated mature donor T lymphocytes in a major histocompatibility complex (MHC) [H2-haplotype] mismatched murine transplant model as a new method to facilitate engraftment of donor CB cells.

Methods:

We analyzed the rates of donor hematopoietic cell engraftment, graft versus host disease (GVHD), and long-term survival in H2 haplotype disparate (C57BL/6®AKR) mice after CBT. Three different experimental groups were transplanted after sublethal radiation. Group 1 received allogeneic full term newborn peripheral blood alone, group 2 was transplanted with the same donor cells and unmanipulated donor T cells, and group 3 was transplanted with the similar donor cells and psoralen (S-59) treated donor T cells.

Results:

We observed a low rate of donor engraftment after transplantation with cord blood alone (Group 1). There was better engraftment but a high rate of fatal GVHD after transplantation with cord blood and unmodified donor T-cells (Group 2). The best results were observed after transplantation with 3 × 106 nucleated cord blood cells and 9 ×106 S-59 treated T cells (Group 3b). The engraftment rate was 75% compared to 12.5% after transplantation with 6 × 106 CB cells alone (p=0.04). The long-term survival in group 3 was 100% and the rate and severity of GVHD were minimal. Engraftment observed after CBT with unmodified donor T-cells (group 2) was accompanied by severe GVHD and poor survival. Donor myeloid, B cells and T cells were documented in the spleen and bone marrow of Group 3 mice by 30 days after CBT, although full hematological recovery was delayed until 50-60 days after CBT.

Conclusions:

These results show improved cord blood engraftment kinetics across a disparate H2 haplotype by adding psoralen-treated donor T lymphocytes. Co-transplantation of psoralen treated lymphocytes with CB cells facilitated durable engraftment of donor MHC high/c-kit+ cells in the marrow and splenic compartments with complete but delayed hematopoietic recovery. The low GVHD risk and excellent long-term survival observed in this murine model suggests the potential for clinical application.

Treatment Group CB dose (× 106T-cell dose (× 106GVHD (score 1–10) Engraftment Survival 
1 (CB alone) 0.5 – 10 1/37 (3) 1/37 (2.7%) 36/37 (97%) 
2 (CB + T) 1.0 – 3.0 3.0 3/8 (6) 3/8 (38%) 4/8 (50%) 
3a (CB + S59T) 0.5 – 3.0 1.0 – 3.0 0/16 1/16 (6.3%) 16/16 (100%) 
3b (CB + S59T) 3.0 9.0 1/8 (3) 6/8 (75%)* 8/8 (100%) 
3c (CB + S59T) 6.0 3.0 0/6 3/6 (50%) 6/6 (100%) 
Treatment Group CB dose (× 106T-cell dose (× 106GVHD (score 1–10) Engraftment Survival 
1 (CB alone) 0.5 – 10 1/37 (3) 1/37 (2.7%) 36/37 (97%) 
2 (CB + T) 1.0 – 3.0 3.0 3/8 (6) 3/8 (38%) 4/8 (50%) 
3a (CB + S59T) 0.5 – 3.0 1.0 – 3.0 0/16 1/16 (6.3%) 16/16 (100%) 
3b (CB + S59T) 3.0 9.0 1/8 (3) 6/8 (75%)* 8/8 (100%) 
3c (CB + S59T) 6.0 3.0 0/6 3/6 (50%) 6/6 (100%) 
*

p value=0.007, compared to group 1 transplanted with similar nucleated cord blood cell dose.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.